msh--4-nle-7-phe-alpha- and Mesothelioma

We have previously reported that the peptide a-melanocyte stimulating hormone (alpha-MSH) has antiproliferative effects in human malignant mesothelioma cells. To determine the molecular mechanisms underlying such effects, we investigated the changes in gene expression profile induced by the alpha-MSH analog [Nle4 -DPhe7 ]-alpha-MSH (NDP-alpha-MSH) in a human malignant mesothelioma cell line. The cDNA macroarray technique revealed changes in expression of genes involved in cell growth, adhesion, signal transduction, and transcription. In particular, NDP-alpha-MSH down-regulated expression of B-Myb and Myc, two oncogenes considered of paramount importance for cell proliferation and cancer. Further, NDP-alpha-MSH exerted a favorable transcriptional regulation of certain integrins and their signaling pathways. Finally, peptide treatment was associated with a prominent inhibition of IL-13, a cytokine with tumor-promoting effects. The data indicate that the influences of alpha-MSH extend beyond the established anti-inflammatory effects in normal cells to include cell cycle regulatory properties in malignant cells.

Topics: alpha-MSH; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cyclin A; Cyclin A2; Cyclin B; Cyclin B1; DNA-Binding Proteins; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Interleukin-13; Mesothelioma; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins c-myc; Reverse Transcriptase Polymerase Chain Reaction; Trans-Activators